Prerequisites: 333 CHEM Linked to course syllabus and “WEB PAGE” synthesis Modified from sides of William Tam & Phillis Chang 29/32

Due the second recitation: (1) Answer the following question in some detail. (2) Complete review work sheet of 333 reactions. What study activity (activities) helped you the most in CHEM 333? Assignments

Text Solomons (10 th ed) Schedule of tests and “ projected ” pace Honor code Policy - grading scale Recitation WEB PAGE Homework problems, aids, etc SYLLABUS “ must read ” (linked to the “ Home ” and WEB Page*) *

CHAPTER 12 Alcohols from Carbonyl Compounds Oxidation-Reduction Organometallic Compounds Srtucture of the carbonyl group C=O addition/ROH oxidation Hydrogenation of “ double bonds ” olefins and carbonyls LiAlH 4 NaBH 4 Oxidation w/ PCC Oxidation w/ H 2 CrO 4 and KMnO 4 Organometallic compounds R-Li & RMgX Organometallics as bases Organometallics as Nu:(-) with: carbonyls epoxides esters Synthesis Chapter 12 CHEM 334

Ch Structure Carbonyl carbon: sp 2 hybridized Planar structure

Ch Structure of the Carbonyl Group, Carbonyl compounds aldehyde alkanal ketone alkanone   Others: Y = OH, OR’, NH 2, X, etc.

Ch Rxs of Carbonyl Compounds with Nucleophiles Rxs of Carbonyl Compounds with Nucleophiles One of the most important reactions: nucleophilic addition to the carbonyl recall:

Ch Two important nucleophiles (bases): Two important reactions: Hydrides (H: (-) from NaBH 4 & LiAlH 4 ) Carbanions (from R: (-)(+) Li & R: (-)(++) Mg (-) X )

Ch Oxidation-Reduction Rxs reduction: increase in hydrogen content or decrease in oxygen content carboxylic acid aldehyde oxygen content decreases hydrogen content decreases oxidation: increase in oxygen content or decrease in hydrogen content

Ch Alcohols by Reduction of Carbonyl Compounds

Ch Alcohols by Reduction of Carbonyl Compounds (1 o alcohol)

Ch Hydrides Nucleophilic and very basic React violently with H 2 O or protic sources Rxs in Et 2 O or THF, reduces all carbonyl groups LiAlH 4 = less reactive & less basic than LiAlH 4 uses protic solvent (e.g. EtOH) reduces only aldehydes and ketones “ LAH ” NaBH 4

Ch Examples skip ether ex

Ch Mechanism (neutralize)

Ch Mechanism Esters (carboxylic acids) are reduced to 1 o alcohols

Ch C.Summary of LiAlH 4 and NaBH 4 Reactivity ease of reduction reduced by NaBH 4 reduced by LiAlH 4

Ch Oxidation of Alcohols Oxidation of Primary (1 o ) Alcohols special CrO 3 reagents stronger oxidants

Ch Special CrO 3 reagent = PCC Reagent p yridinium c hloro c hromate

Ch PCC oxidation 1o1o 3o3o 2o2o No Reaction

Ch Oxidation of 1 o Alcohols to Carboxylic Acids Jones reagent

Ch Oxidation: CrO 3 + H 2 SO 4 [or H 2 CrO 4 ] [or KMnO 4 /HO (-) / Δ then H + /H 2 O]

Ch Organometallic Compounds organometallic compounds contain carbon-metal bonds

Ch Preparation of Organolithium & Organomagnesium Compounds Order of reactivity of RX RI > RBr > RCl

Ch Examples

Ch Rxs with Compounds Containing Acidic Hydrogens Grignard reagents and organolithium compounds are very strong bases

Ch Examples as base + Mg 2+ + Br −

As nucleophiles:

Ch React as nucleophiles with epoxides

Ch Rxs of Grignard & Organolithium Reagents with Carbonyls

Ch examples

Ch Reaction with esters 3 o alcohol

Ch Mechanism

Ch Addition-Elimination

Ch Planning a Grignard [or RLi ] Synthesis Synthesis of

Ch Method 1 Retrosynthetic analysis Synthesis

Ch Method 2 Retrosynthetic analysis Synthesis

Ch Method 3 Retrosynthetic analysis Synthesis

Ch RMgX & RLi reagents cannot be prepared in the presence of the following groups because of reactions (acid-base or nucleophilic addition) :

Ch Sodium or Lithium Alkynides (acetylides) Preparation of lithium alkynides Reaction with aldehydes or ketones

Ch Synthesis and Protecting Groups

Ch Retrosynthetic analysis However disconnection

Ch Need to “ protect ” the –OH group first

Ch Synthesis